Sclareol exerts synergistic antidepressant effects with quercetin and caffeine, possibly suppressing GABAergic transmission in chicks

This study evaluated the effects of sclareol (SCL) with or without caffeine (CAF) and quercetin (QUR) using in -vivo and in-silico studies. For this, 5-day-old chicks weighing between 45 and 48 g were randomly divided into five groups and treated accordingly. The chicks were monitored to compare the occurrence, latency, and duration of sleep as well as the loss and gain of righting reflex in response to SCL-10 mg/kg, CAF-10 mg/kg, and QUR-50 mg/kg using a thiopental sodium (TS)-induced sleeping model. Data were analyzed by one-way ANOVA followed by t-Student-Newman-Keuls' as a posthoc test at 95% confidence intervals with multiple comparisons. An in-silico study was also performed to investigate the possible antidepressant mechanisms of the test and/or standard drugs with different subunits of GABAA receptors. In comparison to the SCL, CAF, and QUR individual groups, SCL+CAF+QUR significantly increased the latency while decreasing the length of sleep. The incidence of loss and gain of the righting reflex was also modulated in the combination group. SCL showed better interaction with GABAA (alpha 2 and alpha 5) subunits than QUR with alpha 2, alpha 3, and alpha 5. All these compounds showed stronger in-teractions with the GABAA receptor subunits than the standard CAF. Taken together, SCL, CAF, and QUR reduced the TS-induced righting reflex and sleeping time in the combination group more than in the individual treat-ments. SCL may show its antidepressant effects, possibly through interactions with GABAA receptor subunits.